Antibiotics such as vancomycin and carbapenems are active against highly-antibiotic resistant bacteria unresponsive to other antibiotics. Overuse of these antibiotics can exert selection pressure and promote colonization and infection with increasingly resistant organisms, raising the specter of morbidity and mortality due to untreatable infection. Vancomycin in particular is commonly used as a first-line choice when infection is suspected in the newborn intensive care unit, despite evidence that there is no survival benefit attributed to empiric therapy for most infected infants. Guidelines have been developed that can safely limit the empiric use of vancomycin to those infants known to be colonized with MRSA.